Biomedical subjects
Publications and source records attributed to M Salcman.
Brain stem hemorrhage was first recorded in 1812. Its origin has been the subject of much study and experimentation. We review the studies that stress mechanical forces because dynamic axial distortion of the brain stem is a major factor in the physiology and pathology of the central nervous system.
Dynamic axial distortion of the brain stem has long been recognized as occurring in the presence of supratentorial mass lesions. Although brain stem hemorrhages occur under these circumstances, the pathophysiology of these hemorrhages is still a matter of controversy. In the present study, the role of the carotid arteries in tethering the brain stem was evaluated during dynamic axial distortion of the neuraxis of the dog. Brain stem hemorrhages occurred in 32 of 48 dogs in which the carotid arteries were left intact (67%) and in only 9 of 46 animals in which the carotid arteries were sectioned (20%). The difference between the two groups is statistically significant (chi 2 = 19.3; P less than 0.001). In this study, we can eliminate intracranial pressure as the primary cause of the lesions because a single variable is present in one series and absent in the other, whereas intracranial pressure and its duration are kept constant. It is concluded that the tethering effect of the carotid arteries is a significant factor in the production of brain stem hemorrhages in the dog by dynamic axial distortion of the brain stem. A selective review of the literature on production of brain stem lesions is provided to support these findings.
While almost no malignant glial tumor can be cured by surgical resection alone, the oncologic benefits of radical tumor removal are clear. Mechanical cytoreduction is the only therapeutic modality by which a two-log cell kill can be achieved quickly. Surgery also "sets up" other therapies by facilitating the patient's survival during the acute treatment phase, by improving the patient's neurologic status, by potentiating the effect of other treatment agents, and through the removal of large numbers of inherently resistant cells. Recently, the value of reoperation also has been demonstrated, confirming its positive effect on survival. Nevertheless, there remain some patients for whom a radical resection is an inappropriate procedure, and reasonable alternatives should always be considered. Of course, glioblastoma multiforme and other intrinsic tumors of the brain are highly complex and heterogeneous lesions that require multimodal therapy, of which surgery is but one component.
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Blood vessels of the fetal, neonatal, and adult subprimate and primate CNS, including circumventricular organs (e.g., median eminence, pituitary gland, etc.), and of solid CNS and nonneural (anterior pituitary gland) allografts placed within brains of adult mammalian hosts were visualized with peroxidase cytochemistry applied in three ways: to tissues from animals injected systemically with native horseradish peroxidase (HRP) or peroxidase conjugated to the lectin wheat germ agglutinin (WGA) prior to perfusion fixation; to tissues from animals infused with native HRP into the aorta subsequent to perfusion fixation; and to tissues from animals fixed by immersion and incubated for endogenous peroxidase activity in red cells retained within blood vessels. In neonatal and adult animals receiving native HRP intravascularly, non-fenestrated vessels contributing to a blood-brain barrier were outlined with HRP reaction product when tetramethylbenzidine (TMB) as opposed to diaminobenzidine (DAB) was used as the chromogen; fenestrated vessels of circumventricular organs were not discernible due to the density of extravascular reaction product. Fenestrated and non-fenestrated cerebral and extracerebral blood vessels exposed to bloodborne WGA-HRP were visible when incubated in TMB and DAB solutions. Native HRP infused into the aorta of fixed animals likewise labeled non- fenestrated vessels throughout the brain upon exposure to TMB or DAB but obscured fenestrated vessels of the circumventricular organs. Endogenous peroxidase activity of red cells, seen equally well with TMB and DAB, outlined blood vessels throughout the cerebral gray and white matter and all circumventricular organs in fetal, neonatal, and adult animals. Application of the three peroxidase cytochemical approaches to study the development or absence of a blood-brain barrier in intracerebral allografts demonstrated that the vascularization of day 16-19 fetal/1 day neonatal CNS allografts is not well defined prior to 7 days following intracerebral placement of the grafts. CNS allografts secured from donor sites expected to possess a blood-brain barrier exhibited blood vessels that were not leaky to HRP injected intravenously in the host. Fenestrated blood vessels associated with anterior pituitary allografts were evident prior to 3 days posttransplantation within the host brain and permitted blood-borne HRP in the host to enter the graft and surrounding host brain parenchyma.
The contribution of tubular profiles within the mammalian cerebral endothelium to the formation of transcellular channels was analysed following exposure of the endothelium to native horseradish peroxidase (HRP) dissolved in saline or dimethyl sulphoxide (DMSO) administered intravenously in mice. Within 5-15 min, but not at 30 min to 2 h postinjection, peroxidase-positive extravasations were evident within the parenchyma of the forebrain and brainstem of mice exposed and not exposed to DMSO. The extravasations may be associated with the rupture of interendothelial tight junctions at the level of arterioles as a consequence of the perfusion-fixation process. Ultrastructural inspection of endothelia within and away from areas of peroxidase extravasation revealed the following intraendothelial, peroxidase-positive organelles: presumptive endocytic vesicles, endosomes (a prelysosomal compartment), multivesicular and dense bodies, and tubular profiles. Statistical analysis of the concentration of HRP-labelled presumptive endocytic vesicles, which may coalesce to form tubules, within endothelia from mice injected intravenously with HRP-DMSO compared to mice receiving HRP-saline revealed no significant difference. HRP-positive tubular profiles were blunt-ended, variable in length and width, and appeared free in the cytoplasm or in continuity with dense bodies. Labelled tubules free in the cytoplasm were positioned parallel to the luminal and abluminal plasma membranes and were less frequently oblique or perpendicular to these membranes. Tubular profiles analysed in serial thin sections or with a goniometer tilt stage did not establish membrane continuities with the luminal and abluminal plasma membranes. Peroxidase-positive tubular profiles were similar morphologically to those exhibiting acid hydrolase activity but did not share morphological and enzyme cytochemical similarities with the endoplasmic reticulum that stained for glucose-6-phosphatase (G6Pase) activity. G6Pase-positive profiles of endoplasmic reticulum were not observed to contribute to a transendothelial canalicular network. Our results suggest that: (i) peroxidase-labelled tubules, acid hydrolase-positive tubules, and G6Pase-positive endoplasmic reticulum do not form transcellular channels through the cerebral endothelium; (ii) tubular profiles labelled with blood-borne HRP in the cerebral endothelium are associated with the endosome apparatus and/or the lysosomal system of organelles; and (iii) DMSO does not appear to alter the permeability of the blood-brain barrier to blood-borne protein.
A bedside lead cubicle was designed to minimize the radiation exposure of intensive care unit staff during routine interstitial brain irradiation by removable, high intensity iridium-192. The cubicle shields the patient without restricting intensive care routines. The design specifications were confirmed by exposure measurements around the shield with an implanted anthropomorphic phantom simulating the patient situation. The cubicle reduces the exposure rate around an implant patient by as much as 90%, with the exposure level not exceeding 0.1 mR/hour/mg of radium-equivalent 192Ir. Evaluation of data accumulated for the past 3 years has shown that the exposure levels of individual attending nurses are 0.12 to 0.36 mR/mg of radium-equivalent 192Ir per 12-hour shift. The corresponding range for entire nursing teams varies between 0.18 and 0.26. A radiation control index (exposure per mg of radium-equivalent 192Ir per nurse-hour) is thus defined for individual nurses and nursing teams; this index is a significant guide to the planning of nurse rotations for brain implant patients with various 192Ir loads. The bedside shield reduces exposure from 192Ir implants by a factor of about 20, as expected, and the exposure from the lower energy radioisotope iodine-125 is barely detectable.
Early diagnosis is essential to successful treatment of a brain tumor. Early general signs, such as headache, seizures and psychologic changes, are followed by specific localizing signs that can be elicited by meticulous neurologic examination. A computed tomographic scan should be obtained long before signs of increased intracranial pressure appear. New modes of treatment have increased both the length and the quality of survival.
Pathways traversed by peripherally administered protein tracers for entry to the mammalian brain were investigated by light and electron microscopy. Native horseradish peroxidase (HRP) and wheat germ agglutinin (WGA) conjugated to peroxidase were administered intranasally, intravenously, or intraventricularly to mice; native HRP was delivered intranasally or intravenously to rats and squirrel monkeys. Unlike WGA-HRP, native HRP administered intranasally passed freely through intercellular junctions of the olfactory epithelia to reach the olfactory bulbs of the CNS extracellularly within 45-90 minutes in all species. The olfactory epithelium labeled with intravenously delivered HRP, which readily escaped vasculature supplying this epithelium. Blood-borne peroxidase also exited fenestrated vessels of the dura mater and circumventricular organs. This HRP in the mouse, but not in the other species, passed from the dura mater through patent intercellular junctions within the arachnoid mater; in time, peroxidase reaction product in the mouse brain was associated with the pial surface, the Virchow-Robin spaces of vessels penetrating the pial surface, perivascular clefts, and with phagocytic pericytes located on the abluminal surface of superficial and deep cerebral microvasculature. Blood-borne HRP was endocytosed avidly at the luminal face of the cerebral endothelium in all species. WGA-HRP and native HRP delivered intraventricularly to the mouse were not endocytosed appreciably at the abluminal surface of the endothelium; hence, the endocytosis of protein and internalization of cell surface membrane within the cerebral endothelium are vectorial. The low to non-existent endocytic activity and internalization of membrane from the abluminal endothelial surface suggests that vesicular transport through the cerebral endothelium from blood to brain and from brain to blood does not occur. The extracellular pathways through which probe molecules enter the mammalian brain offer potential routes of passage for blood-borne and air-borne toxic, carcinogenic, infectious, and neurotoxic agents and addictive drugs, and for the delivery of chemotherapeutic agents to combat CNS infections and deficiency states. Methodological considerations are discussed for the interpretation of data derived from application of peroxidase to study the blood-brain barrier.
We have conducted a phase-I clinical trial of CT-guided stereotactic implantation of Ir192 in the treatment of malignant astrocytomas. During the past year, 16 patients have been implanted with two to four catheters in the residual enhancing portion of their tumor. These patients represent 50% of our total experience with the CT compatible Leksell frame. Each catheter contains three to six high intensity (2.0 to 2.5 mg Ra equivalent) seeds with 0.5 cm separation between the sources. The total activity of Ir192 per implant has been 30-65 mg radium equivalent. In the 16 patients, 49 catheters have been placed, an average of three targets calculated per patient and no targets have been missed. The radiation exposure to personnel has been surveyed in detail and drops off to less than 2 mr/h six feet from the patient when our custom-built radiation shield is employed. We have reserved permanent implantation of I125 for patients with tumors in unusual locations (e.g. pineal) or for individuals with slowly growing non-gliomatous lesions (i.e. meningioma). The tumor volumes have ranged from 12-120 cm3. Unique aspects of our implant procedure include the use of a Leksell frame already adapted to the GE-8800 scanner, the use of pre- and post-implant computerized treatment planning programs to determine the dose distribution profiles and the use of adjustable metal collars crimped to the outer catheters to provide ease of insertion, uniform pre-implant catheter length, and protection against source migration. Two of our patients have suffered from subacute radiation reactions, primarily due to delayed cerebral edema and both of these cases have largely resolved.(ABSTRACT TRUNCATED AT 250 WORDS)
The relative importance or utility of the carbon dioxide laser within the total context of multimodality therapy and in comparison to conventional surgical techniques is unknown. Over a 36 month period, 421 operations for tumors of the brain and spinal cord were performed in our clinic. Of these, 111 (26%) were carried out with the aid of the laser. After excluding stereotactic and transsphenoidal operations, a comparison was made between 105 laser and 216 non-laser craniotomies. With the exception of pituitary tumors, the most frequent diagnoses in both the laser and non-laser cases were the same: malignant astrocytoma (48.6 vs 33.9%), meningioma (11.4 vs 14.2%) and low grade astrocytoma (8.6 vs 8.7%). The number of reoperations in the laser group (60.1%) was higher than in the non-laser group (32.7%; p less than 0.000001) and the mean operating time (299 minutes vs 237 minutes; p less than 0.00001) was longer, but there was no significant mean difference in mortality, CNS morbidity, mean blood loss (638 ml vs 671 ml) or mean length of stay (23 vs 25 days). For the subgroup of 134 cases of malignant astrocytoma, 82% of laser procedures were reoperations versus 50% for non-laser cases (p less than 0.0002) and the mean operating time was slightly longer (p less than 0.02). The length of stay for laser cases tended to be less (21 vs 27 days; p less than 0.04), but there was again no difference in blood loss (457 ml vs 522 ml), CNS morbidity (7.8 vs 4.8%) or mortality.(ABSTRACT TRUNCATED AT 250 WORDS)
A 28-year-old man presented with hydrocephalus due to an infection by Cryptococcus neoformans involving his ventriculoatrial shunt. Ultrastructural studies of the ventriculoatrial shunt demonstrated yeastlike organisms consistent with C. neoformans within a biofilm on the appliance. Quantitative microbiological studies of segments of the shunt demonstrated C. neoformans in a concentration gradient from 9 X 10(6) colony-forming units (CFU)/0.5-cm section involving the ventricular portion of the catheter to 1 X 10(2) CFU/0.5-cm section at the vascular tip. The clinical, microbiological, and ultrastructural data suggest that this cryptococcal infection started as a ventriculitis or encephalitis with extension to the meningeal surface. Future application of these methods may further elucidate the pathogenesis of ventriculoatrial shunt infections.
The patient described in this article had a large skull defect under the scalp which had been irradiated during treatment of a malignant brain tumor. The patient desired reconstruction of her defect. To provide good soft-tissue coverage for the bony reconstruction, a free latissimus dorsi musculocutaneous flap was used. The bony defect was partially reconstructed with split-rib grafts. The two parts of the reconstruction were combined into one operation, since it was felt that the well-vascularized muscle would ensure viability of the bone grafts.
Simultaneous recordings were made from small collections (2-7) of spontaneously active single units in the striate cortex of unanesthetized cats, by means of chronically implanted electrodes. The recorded spike trains were computer scanned for bursts of spikes, and the bursts were catalogued and studied. The firing rates of the neurons ranged from 0.16 to 32 spikes/s; the mean was 8.9 spikes/s, the standard deviation 7.0 spikes/s. Bursts of spikes were assigned a quantitative measure, termed Poisson surprise (S), defined as the negative logarithm of their probability in a random (Poisson) spike train. Only bursts having S greater than 10, corresponding to an occurrence rate of about 0.01 bursts/1,000 spikes in a random spike train, were considered to be of interest. Bursts having S greater than 10 occurred at a rate of about 5-15 bursts/1,000 spikes, or about 1-5 bursts/min. The rate slightly increased with spike rate; averaging about 2 bursts/min for neurons having 3 spikes/s and about 4.5 bursts/min for neurons having 30 spikes/s. About 21% of the recorded units emitted significantly fewer bursts than the rest (below 1 burst/1,000 spikes). The percentage of these neurons was independent of spike rate. The spike rate during bursts was found to be about 3-6 times the average spike rate; about the same for longer as for shorter bursts. Bursts typically contained 10-50 spikes and lasted 0.5-2.0 s. When the number of spikes in the successively emitted bursts was listed, it was found that in some neurons these numbers were not distributed at random but were clustered around one or more preferred values. In this sense, bursts occasionally "recurred" a few times in a few minutes. The finding suggests that neurons are highly reliable. When bursts of two or more simultaneously recorded neurons were compared, the bursts often appeared to be temporally close, especially between pairs of neurons recorded by the same electrode; but bursts seldom started and ended simultaneously on two channels. Recurring bursts emitted by one neuron were occasionally accompanied by time-locked recurring bursts by other neurons.
Posttraumatic aneurysms of the proximal intracranial internal carotid artery are rare. A case is presented in which the evolution and regression of such an aneurysm is documented by computed tomography as well as by arteriography. The coexistence of a proximal dissection of the cervical carotid artery probably contributed to the growth of the aneurysm.
We describe a patient with a gunshot wound to the brain that traversed the left cerebellar hemisphere and terminated in the left lateral midpons. The clinical findings, operative course, neuroradiographic features, and evoked potential data are correlated with the functional anatomy of the pons. It is possible to demonstrate that a local lesion in the lateral pons causes a hemiparesis, worse in the upper extremity, thus suggesting a somatotopic localization of the pontine corticospinal tract not previously described.
A case of a cholesterol granuloma located in the petrous apex and eroding into the sphenoidal sinus is reported. Cholesterol granuloma is thought to occur when pneumatized cells in the temporal bone become obstructed. Although usually occurring in the middle ear, it can occur in the petrous apex. The diagnosis and surgical management are discussed.
Advances in chemotherapy have increased the indications for insertion of cerebrospinal fluid (CSF) reservoirs in the treatment of both primary and secondary central nervous system neoplasia. There have been no recent evaluations of the current indications and complications of this procedure in a general neurooncology practice. We undertook a retrospective review of our total experience of 60 patients who were implanted with CSF reservoirs between November 1977 and October 1983. The mean age of those implanted was 38 years (range, 22 months to 79 years). The reasons for insertion were: drug instillation, 35 cases (58.3%); drug level monitoring, 15 cases (25.0%); intermittent tumor cyst drainage, 6 cases (15.0%); and syrinx drainage, 1 case (1.6%). Drug level monitoring was most often done in conjunction with specific experimental chemotherapy protocols. There were no complications after primary insertion, but 9 of 60 reservoirs (15%) required revision for technical failure. Revision was much more likely to occur in the presence of an intracranial mass lesion (7 of 34, or 20.5%). The revision rate in cases of meningeal carcinomatosis was only 7.6% (2 of 26). Patients requiring revision included 5 with glioblastoma, 2 with metastatic tumors, and 2 with meningeal carcinomatosis. Four of the 9 patients requiring revisions developed complications (44%). There were three infections with positive CSF cultures and one subdural hematoma. Infected patients included those with multiple craniotomies, prior cranial irradiation, or some form of chemotherapy. We conclude that primary insertion of a CSF reservoir in a patient with neoplastic involvement of the central nervous system is extremely safe, that technical failure tends to occur in the presence of mass lesions, and that the complication rate of repeated insertion is quite high.